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 Table of Contents  
ARTICLE
Year : 2014  |  Volume : 3  |  Issue : 2  |  Page : 127-131

Profile and determinants of treatment failure among smear-positive pulmonary tuberculosis patients in Ebonyi, Southeastern Nigeria


1 National Tuberculosis and Leprosy Control Programme, Ministry of Health, Abakaliki, Ebonyi State, Nigeria
2 Centre for Development and Reproductive Health, Enugu, Nigeria
3 Department of Internal Medicine, Federal Teaching Hospital, Abakaliki, Ebonyi State, Nigeria

Date of Web Publication26-Feb-2017

Correspondence Address:
Kingsley N Ukwaja
Department of Internal Medicine, Federal Teaching Hospital, Abakaliki, Ebonyi State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.ijmyco.2014.02.005

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  Abstract 


Background: Early identification of determinants of tuberculosis (TB) treatment failure is urgently needed in resource-limited settings. This study describes the profile and determinants of TB treatment failure in a high-incidence setting where patients were managed at a TB control program with significant resource limitations.
Methods: This was a retrospective case-control study carried out in one tertiary and one secondary hospital in Southeastern Nigeria. Cases were adult (≥15 years) TB patients with a positive sputum smear after 5 months of treatment (treatment failure). Controls were adult TB patients whose sputum smear was positive at the beginning of the treatment but who were smear-negative in the last month of treatment and on at least one previous occasion (cured). Cases were compared with controls to assess determinants of treatment failure.
Results: Of the 1668 TB patients registered during the study period, 985 (59%) had smear-positive pulmonary TB. Of these, 694 (70.5%) were aged ≤40 years, 602 (61.1%) were males, 707 (71.8%) were rural residents, and 898 (91.2%) received care at the private facility. The prevalence of treatment failure was 2.5%. Significant determinants of treatment failure were: older age (>40 years) (P< 0.001), male gender (P = 0.04), previous treatment for TB (P = 0.045), and positive sputum smears after two month of anti-tuberculosis treatment (0.001).
Conclusion: This study showed that the treatment failure rate among smear-positive TB patients is low in Nigeria. Education and improved clinical and laboratory interventions for the identified at-risk groups may reduce TB treatment failure in resource-limited settings.

Keywords: Tuberculosis, Epidemiology, Predictors, Treatment failure, Unsuccessful outcomes, Nigeria


How to cite this article:
Alobu I, Oshi DC, Oshi SN, Ukwaja KN. Profile and determinants of treatment failure among smear-positive pulmonary tuberculosis patients in Ebonyi, Southeastern Nigeria. Int J Mycobacteriol 2014;3:127-31

How to cite this URL:
Alobu I, Oshi DC, Oshi SN, Ukwaja KN. Profile and determinants of treatment failure among smear-positive pulmonary tuberculosis patients in Ebonyi, Southeastern Nigeria. Int J Mycobacteriol [serial online] 2014 [cited 2020 Feb 17];3:127-31. Available from: http://www.ijmyco.org/text.asp?2014/3/2/127/200942




  Introduction Top


Tuberculosis (TB) control remains a global challenge especially in high-burden countries where resources are limited, human immunodeficiency virus (HIV) co-infection is high, and control efforts are being threatened by drug-resistant TB [1],[2]. The World Health Organisation (WHO) currently recommends a case detection rate of 70% and a treatment success rate of 85% for all TB cases [1]. It is believed that achieving these targets will lead to a reduction in TB prevalence, incidence, transmission and drug resistance to TB [3].

An important indicator recommended by the WHO for the monitoring of TB control efforts is the proportion of pulmonary TB patients whose sputum smear or culture are positive after 5 months or later during treatment [4]. These individuals are classified as treatment failure cases. Treatment failure is a serious problem for National TB control programs because cases tend to have higher morbidity and mortality compared with those who are cured [5]. Also, they remain infectious for prolonged periods of time; hence, affected patients continue to transmit the disease in the community [5]. In addition, very high rates of multidrug-resistant TB have been found among treatment failure cases in resource-limited settings [6].

The identification of factors associated with treatment failure is a priority for TB control programs because this may help in the early institution of interventions for at-risk TB patients in order to improve treatment targets [4]. Few studies done in other settings have shown that predictors of treatment failure may include social, radiological, laboratory and treatment-related factors [7],[8],[9],[10]. As these factors can vary in different populations and health systems, it is important to assess the situation in specific settings. No study has been carried out to identify the determinants of treatment failure in this setting. This study is aimed at determining the burden and predictors of TB treatment failure in smear-positive pulmonary TB patients in Southeastern Nigeria.


  Materials and methods Top


Study design and setting

The study was conducted in one tertiary (public) and one secondary (private/not-for-profit mission) hospital in Ebonyi State, Southeastern Nigeria. A retrospective unmatched case-control study design was used to assess adult smear-positive pulmonary TB patients who registered for treatment at the study sites between 1 January 2011 and 31 December 2012. Cases were smear-positive pulmonary TB aged ≥15 years who had a positive sputum smear at 5 months and were classified as treatment failure after treatment (cases). Controls were adult pulmonary TB patients whose sputum smear was positive at the beginning of the treatment, but who were smear-negative in the last month of treatment and on at least one previous occasion [11],[12].

Diagnosis and treatment of TB and HIV

Adult patients suspected of having TB undergo sputum acid-fast-bacilli (AFB) microscopy [11],[12]. Patients with AFB in at least one of the three smears submitted are registered as smear-positive pulmonary TB. All adults suspected of having TB undergo HIV counseling and testing at the time of submission of sputum for AFB [12]. The NTP in Ebonyi State phased out the 8-month anti-TB regimen (consisting of 2 months of rifampicin [R], isoniazid [H], pyrazinamide [Z] and ethambutol [E]/6 months of ethambutol and isoniazid [2RHZE/6EH]) in the 2011 cohort [12]. All adult TB patients diagnosed in 2012 were treated using the 6-month anti-tuberculosis regimen consisting of: 2-month RHZE/and 4-month RH [2RHZE/4RH]. All the patients receive community directly observed treatment short course (DOTS). All HIV-infected TB patients are offered trimethoprim/sulfamethoxazole (cotrimoxazole prophylactic treatment [CPT]) to prevent other opportunistic infections. HIV treatment follows national and WHO guidelines with antiretroviral therapy initiated between two weeks and two months of commencing anti TB treatment [12].

Data collection and analysis

Using a standardized form, data about all smear-positive TB patients treated at the participating centers were extracted. Information collected included: registration status; age; gender; residence; regimen received; and treatment outcome. The standard WHO definitions were used for TB disease classification, registration and treatment outcome categories (cured, completed treatment, failure, defaulted treatment, died and transferred out) [11],[12]. TB registration status was divided into ‘new’ or ‘previously treated’.

Statistical analyses were performed using Epi Info (Epi Info version 3.4.1; Centers for Disease Control and Prevention, Atlanta, GA, USA). Univariate analyses were performed to describe the baseline characteristics of the participants and were reported as proportions and means. Categorical groups' comparisons were performed using the Chi-square tests, and the Fisher's exact test was used for an expected cell value frequency less than five. Multivariable logistic regression analysis showed unstable models and were therefore excluded. AP value of < 0.05 was considered significant.

The study was approved by the Ethics and Research Advisory Committee of the National Tuberculosis and Leprosy Control Programme, Ministry of Health, Ebonyi State.


  Results Top


Of the 1668 TB patients registered during the study period, 985 (59%) had smear-positive pulmonary TB. Of these, 694 (70.5%) were aged ≤40 years, 602 (61.1%) were males, 707 (71.8%) were rural residents and 898 (91.2%) received care at the private facility. Also, 928 (94.2%) of the cases were registered as new cases, 470 (47.7%) were treated with the current 6-month rifampicin containing regimen, and 136 (13.8%) were HIV positive ([Table 1]). Overall, 797 (80.9%) of the participants were cured, 98 (9.9%) defaulted, 57 (5.8%) died, 25 (2.5%) had treatment failure, and 8 (0.8%) were transferred out.
Table 1: Baseline characteristics of 985 patients with smear-positive tuberculosis who were treated at the study sites in Ebonyi State, Nigeria 2011–2012.

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Serial sputum AFB results of the study participants are shown in [Table 2]; 985 patients were sputum smear-positive at entry, and of these, 187 (19%) were smear-positive after intensive treatment with RHZE for two months, and 25 (2.5%) remained positive after 5 months of treatment. Therefore, the prevalence of treatment failure was 2.5% (proportion with a positive sputum smear after 5 months of treatment). The treatment failure rate among patients who were HIV positive was 5/131 (3.7%) compared with 20/849 (2.4%) among those that were HIV negative (P = 0.36).
Table 2: Serial sputum smear results of the study participants who were smear positive at entry (n = 985).

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The analysis of factors associated with treatment failure is as shown in [Table 3]. The predictors of treatment failure were: older age (>40 years) (P< 0.001), male gender (P = 0.04), previous treatment for TB (P = 0.045) and positive sputum smears after two months of anti-tuberculosis treatment (P = 0.001).
Table 3: Analysis of demographic and clinical factors associated with treatment failure during anti-tuberculosis therapy in Ebonyi State, Nigeria 2011–2012.

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  Discussion Top


In this study, it was shown that TB affects mainly the young age group in this setting unlike high-income settings where the elderly are the mostly affected group [13]. This finding has been demonstrated in other resource-limited settings, and it has a negative impact on the economy as a substantial proportion of the workforce are not strong enough to contribute to socio-economic development. Also, a higher proportion of patients with smear-positive were males; this agrees with findings in northeastern and southwestern Nigeria [8],[14] and indicates the need to improve diagnosis of TB among women.

The cure rate of 80.9% in these patients was below the 85% target recommended by the WHO guidelines [11]. This suggests that more efforts are needed to further improve the treatment success rate of TB care in this setting. This will require reducing the default rate and the mortality rates in this region. The treatment failure rate in this study was 2.5%; this agrees with the findings in Egypt where the treatment failure ranged between 0.9% and 5.1% but was lower than a failure rate of 5% and 22.6% found in tertiary hospital settings in southwestern and northwestern Nigeria respectively [7],[8],[14].

In this study, it was shown that older age was a determinant for treatment failure. This was unlike findings from Uganda and Egypt which showed no differences in age [7],[9]. The reasons for these differences are not clear. However, older TB patients has been suggested to be at risk of increased physical disability resulting in increased delay in clearing the Mycobacterium bacilli probably due to decreasing immunity and also delay in seeking care and diagnosis which might lead to worsening of the disease [15]. Also, this study shows that male gender was a determinant of treatment failure. This is consistent with findings from Brazil, but was contrary to observations in Uganda and Egypt [7],[9],[10]. This suggests that male smear-positive TB patients need to be monitored closely for improved adherence during TB treatment.

A positive sputum smear at 2 months of TB treatment was found to be a strong determinant of treatment failure in this study. This is in agreement with findings in Peru and Uganda [9],[16]. This is an important observation since sputum smear microscopy after two months is routinely carried out in the national TB programs. Thus, TB control programs may use individuals classified as having persistent smear positivity after two months of treatment to identify patients at-risk of treatment failure who may benefit from interventions for the prevention of treatment failure. A study in Peru found that 93.8% of culture-positive TB patients with treatment failure had active pulmonary multidrug-resistant TB [6]. Thus, patients found to have persistent smear positivity after two months of treatment should be investigated further using sputum culture and be treated further based on drug sensitivity testing.

This study also found that previous treatment for TB was a determinant for treatment failure. The current national guidelines recommend that previously treated patients undergo retreatment with the same drugs with the addition of streptomycin in the first two months [12]. As retreatment failure is most common among patients who had a failed initial treatment [17], this underscores the need for further investigation for the presence drug-resistant TB among all previously treated TB patients in Nigeria and other developing countries, and to treat them based on drug susceptibility testing. Other factors found to predict the occurrence of TB treatment failure in other studies include: non-compliance to treatment, deficient health education of patients about TB disease, poor patient knowledge regarding the disease, and diabetes mellitus as a co-morbid condition [7],[8],[9],[10],[18]. These need to be evaluated in future studies.

This study had some limitations. The data was retrospectively collected from TB treatment registers. This study does not have additional data to confirm or refute the findings. In addition, there is no information on participants' knowledge of TB, TB treatment adherence, quality of education given the patient, co-morbid conditions like diabetes mellitus, and anti-TB drug side effects; these factors may affect TB treatment outcome. A qualitative study among patients who failed TB treatment will improve upon these limitations.


  Conclusion Top


This study showed that the treatment failure rate among smear-positive TB patients is low in Nigeria, and its determinants are older age, male gender, previous TB treatment and persistent smear positivity after two months of treatment. TB control efforts in resource-constrained settings should target reducing TB treatment failure. This may require additional interventions like community and patient education to improve knowledge about TB, and sputum culture and drug sensitivity testing for individuals previously treated for TB or with persistent smear positivity after two months of treatment.


  Authors' contributions Top


DCO, SNO, IA and KNU conceived the study; KNU designed the study protocol; DCO, IA and KNU collected data, performed data entry and carried out the data analysis and interpretation; DCO, IA and KNU drafted the manuscript; DCO, SNO and KNU critically revised the manuscript for intellectual content. All authors read and approved the final manuscript. KNU is guarantor of the paper.


  Funding Top


This research was supported through an operational research grant, which is a component of the Wave 3 TBREACH grant from the WHO/Stop TB Partnership with funds from the Canadian International Development Agency (CIDA). The funding source had no role in the study design; the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.


  Competing interests Top


There is no competing interest to declare.


  Acknowledgments Top


We acknowledge all the Staff of the National Tuberculosis Control Programme, Ebonyi State, the Centre for Development and Reproductive Health (CDRH) and all health workers who participated in the meticulous data collection and reporting for their contributions.



 
  References Top

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World Health Organisation. Profiles of High burden countries. WHO Report 2007, Global Tuberculosis control, surveillance, planning, financing. Annex 1:145–148. http://www.who.int/ tb/publications/global_report/2009/pdf/chat1.pdf (accessed 25.01.2014).  Back to cited text no. 1
    
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K. Sadacharam, P. Gopi, S. Chandrasekaran, et al, Status of smear TB patients at 2–3 years after initiation of treatment under a DOTS programme, Ind. J. Tuberc. 54 (2007) 199–203.  Back to cited text no. 5
    
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M.C. Becerra, J. Freeman, J. Bayona, et al, Using treatment failure under effective directly observed short course chemotherapy programme to identify patients with Multi drug resistant tuberculosis, Int. J. Tuberc. Lung Dis. 4 (2000) 108–114.  Back to cited text no. 6
    
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A.M. Morsy, H.H. Zaher, M.H. Hassan, A. Shouman, Predictors of treatment failure among tuberculosis patients under DOTS strategy in Egypt, East. Mediterr. Health J. 9 (2003) 689–701.  Back to cited text no. 7
    
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Y.B. Jibrin, A.B. Ali, S.T. Saad, P.M. Kolo, Prevalence of treatment failure among pulmonary tuberculosis patients in Federal medical centre, Gombe, Northeastern Nigeria, ISRN Infect. Dis. 461704 (2013).  Back to cited text no. 8
    
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E. Namukwaya, F.N. Nakwagala, F. Mulekya, H. Mayanja- Kizza, R. Mugerwa, Predictors of treatment failure among pulmonary tuberculosis patients in Mulago Hospital, Uganda, Afr. Health Sci. 11 (2011) S105–S111.  Back to cited text no. 9
    
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M.F. de Albuquerque, R.A. Ximenes, S. Lucena, et al, Factors associated with treatment failure, drop out, and death in a cohort of tuberculosis patients in Recife, Pernamubuco State, Brazil Cad. Saude Publica 23 (2007) 1573–1582.  Back to cited text no. 10
    
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World Health Organisation, Treatment of Tuberculosis Guidelines, fourth ed., World Health Organization, Geneva, Switzerland, 2010. WHO/HTM/TB/2009.420.  Back to cited text no. 11
    
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Federal Ministry of Health, Department of Public Health, National Tuberculosis and Leprosy Control Programme: Workers Manual, fifth ed., Federal Ministry of Health, Abuja, Nigeria, 2010.  Back to cited text no. 12
    
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P.D.O. Davies, The effects of poverty and ageing on the increase in tuberculosis, Monaldi Arch. Chest Dis. 54 (1999) 168–171.  Back to cited text no. 13
    
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O.E. Amoran, Determinants of treatment failure among tuberculosis patients on directly observed therapy in rural primary health care centres in Ogun State, Nigeria, Prim. Health Care 1 (2011) 104.  Back to cited text no. 14
    
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A. Babali, S. Kiziltas, H. Arda, et al, Factors affecting smear conversion in tuberculosis management, Med. Sci. 1 (2012) 351–362.  Back to cited text no. 15
    
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A.M. Chavez Pachas, R. Blank, M.C. Smith Fawzi, J. Bayona, M.C. Becerra, C.D. Mitnick, Identifying early treatment failure on category I therapy for pulmonary tuberculosis in Lima Ciudad, Peru, Int. J. Tuberc. Lung Dis. 8 (2004) 52–58.  Back to cited text no. 16
    
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K.E. Dooley, O. Lahlou, I. Ghali, J. Knudsen, M.D. Elmessaoudi, et al, Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco, BMC Public Health 11 (2011) 140.  Back to cited text no. 17
    
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C. Lienhardt, K. Manneh, V. Bouchier, et al, Factors determining the outcome of treatment of adult smearpositive cases in The Gambia, Int. J. Tuberc. Lung Dis. 2 (1998) 712–718.  Back to cited text no. 18
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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